Publications by authors named "Min Du"

366 Publications

The effect of influenza virus infection on pregnancy outcomes: A systematic review and meta-analysis of cohort studies.

Int J Infect Dis 2021 Feb 26. Epub 2021 Feb 26.

Research Center of Clinical Epidemiology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100083, China.

Background: Adverse pregnancy outcomes are risk factors for neonatal mortality and morbidity. While some studies have demonstrated notable associations between influenza and adverse pregnancy outcomes, the findings have contrasted with other studies. This meta-analysis was conducted to assess the effect of influenza infection on pregnancy outcomes.

Methods: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to 4 November 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random-effects or fixed-effects models.

Results: A total of 17 studies involving 2,351,204 participants were included. Influenza infection increased the risk of stillbirth (RR = 3.62, 95% CI: 1.60-8.20), with no significant effect on preterm birth (RR = 1.17, 95%CI: 0.95-1.45), fetal death (RR = 0.93, 95%CI: 0.73-1.18), small for gestational age (SGA) (RR = 1.10, 95%CI: 0.98-1.24) and low birth weight (LBW) (RR = 1.88, 95%CI: 0.46-7.66). In a subgroup analysis of LBW, the association was evident in studies conducted during the 2009 H1N1 pandemic (RR = 2.28, 95%CI: 1.81-2.87), with no evidence of an association in pre-pandemic or post-pandemic studies.

Conclusions: Influenza virus infection was associated with an increased risk of stillbirth, but its effect on preterm birth, fetal death, SGA and LBW is still uncertain.
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http://dx.doi.org/10.1016/j.ijid.2021.02.095DOI Listing
February 2021

Diagnosis of Patellofemoral Pain Syndrome Based on a Multi-Input Convolutional Neural Network With Data Augmentation.

Front Public Health 2021 11;9:643191. Epub 2021 Feb 11.

College of Physics and Information Engineering, Fuzhou University, Fuzhou, China.

Patellofemoral pain syndrome (PFPS) is a common disease of the knee. Despite its high incidence rate, its specific cause remains unclear. The artificial neural network model can be used for computer-aided diagnosis. Traditional diagnostic methods usually only consider a single factor. However, PFPS involves different biomechanical characteristics of the lower limbs. Thus, multiple biomechanical characteristics must be considered in the neural network model. The data distribution between different characteristic dimensions is different. Thus, preprocessing is necessary to make the different characteristic dimensions comparable. However, a general rule to follow in the selection of biomechanical data preprocessing methods is lacking, and different preprocessing methods have their own advantages and disadvantages. Therefore, this paper proposes a multi-input convolutional neural network (MI-CNN) method that uses two input channels to mine the information of lower limb biomechanical data from two mainstream data preprocessing methods (standardization and normalization) to diagnose PFPS. Data were augmented by horizontally flipping the multi-dimensional time-series signal to prevent network overfitting and improve model accuracy. The proposed method was tested on the walking and running datasets of 41 subjects (26 patients with PFPS and 15 pain-free controls). Three joint angles of the lower limbs and surface electromyography signals of seven muscles around the knee joint were used as input. MI-CNN was used to automatically extract features to classify patients with PFPS and pain-free controls. Compared with the traditional single-input convolutional neural network (SI-CNN) model and previous methods, the proposed MI-CNN method achieved a higher detection sensitivity of 97.6%, a specificity of 76.0%, and an accuracy of 89.0% on the running dataset. The accuracy of SI-CNN in the running dataset was about 82.5%. The results prove that combining the appropriate neural network model and biomechanical analysis can establish an accurate, convenient, and real-time auxiliary diagnosis system for PFPS to prevent misdiagnosis.
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http://dx.doi.org/10.3389/fpubh.2021.643191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902860PMC
February 2021

Discovery of exolytic heparinases and their catalytic mechanism and potential application.

Nat Commun 2021 02 24;12(1):1263. Epub 2021 Feb 24.

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, China.

Heparinases (Hepases) are critical tools for the studies of highly heterogeneous heparin (HP)/heparan sulfate (HS). However, exolytic heparinases urgently needed for the sequencing of HP/HS chains remain undiscovered. Herein, a type of exolytic heparinases (exoHepases) is identified from the genomes of different bacteria. These exoHepases share almost no homology with known Hepases and prefer to digest HP rather than HS chains by sequentially releasing unsaturated disaccharides from their reducing ends. The structural study of an exoHepase (BIexoHep) shows that an N-terminal conserved DUF4962 superfamily domain is essential to the enzyme activities of these exoHepases, which is involved in the formation of a unique L-shaped catalytic cavity controlling the sequential digestion of substrates through electrostatic interactions. Further, several HP octasaccharides have been preliminarily sequenced by using BIexoHep. Overall, this study fills the research gap of exoHepases and provides urgently needed tools for the structural and functional studies of HP/HS chains.
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http://dx.doi.org/10.1038/s41467-021-21441-8DOI Listing
February 2021

Association between biomass fuel use and the risk of cognitive impairment among older populations in China: a population-based cohort study.

Environ Health 2021 Feb 24;20(1):21. Epub 2021 Feb 24.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No.38, Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Cohort studies on the impact of biomass fuel use for cooking on cognitive impairment among older population are still lacking in China and elsewhere. The aim of this study was to examine whether biomass fuel use for cooking is associated with cognitive impairment in Chinese adults aged 65 years or older.

Methods: The prospective population-based cohort study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) included participants aged 65 years or older in 2014 who were followed-up until 2018 in 23 provinces in China. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and cognitive impairment was defined as total MMSE scores less than 18. The association between biomass fuel use and cognitive impairment was evaluated using the Cox proportional hazards model.

Results: Of the 4145 participants included at baseline, participants who reported that they used biomass fuel for cooking (40.43%; IR: 3.11 versus 2.77 per 100 person-years; aHR: 1.27, 95% CI: 1.02-1.58) had a higher risk of cognitive impairment compared with participants who used clean fuels (53.75%). A stratified analyses showed greater effect estimates of cognitive impairment in the older people that lived in the rural areas (aHR: 1.444, 95% CI: 1.08-3.90) and never smoked (aHR: 1.33, 95% CI: 1.04-1.71).

Conclusions: These findings demonstrated that biomass fuel used for cooking was associated with cognitive impairment, as defined by MMSE, in a population-based study of elderly in China. To prevent cognitive impairment, the structure of cooking fuels requires improvements.
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http://dx.doi.org/10.1186/s12940-021-00706-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905553PMC
February 2021

Association between the COVID-19 pandemic and the risk for adverse pregnancy outcomes: a cohort study.

BMJ Open 2021 02 23;11(2):e047900. Epub 2021 Feb 23.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China

Objectives: The secondary impacts of the COVID-19 pandemic on adverse maternal and neonatal outcomes remain unclear. In this study, we aimed to evaluate the association between the COVID-19 pandemic and the risk for adverse pregnancy outcomes.

Design: We conduced retrospective analyses on two cohorts comprising 7699 pregnant women in Beijing, China, and compared pregnancy outcomes between the pre-COVID-2019 cohort (women who delivered from 20 May 2019 to 30 November 2019) and the COVID-2019 cohort (women who delivered from 20 January 2020 to 31 July 2020). The secondary impacts of the COVID-2019 pandemic on pregnancy outcomes were assessed by using multivariate log-binomial regression models, and we used interrupted time-series (ITS) regression analysis to further control the effects of time-trends.

Setting: One tertiary-level centre in Beijing, China PARTICIPANTS: 7699 pregnant women.

Results: Compared with women in the pre-COVID-19 pandemic group, pregnant women during the COVID-2019 pandemic were more likely to be of advanced age, exhibit insufficient or excessive gestational weight gain and show a family history of chronic disease (all p0.05). After controlling for other confounding factors, the risk of premature rupture of membranes and foetal distress was increased by 11% (95% CI, 1.04 to 1.18; p<0.01) and 14% (95% CI, 1.01 to 1.29; p<0.05), respectively, during the COVID-2019 pandemic. The association still remained in the ITS analysis after additionally controlling for time-trends (all p<0.01). We uncovered no other associations between the COVID-19 pandemic and other pregnancy outcomes (p>0.05).

Conclusions: During the COVID-19 pandemic, more women manifested either insufficient or excessive gestational weight gain; and the risk of premature rupture of membranes and foetal distress was also higher during the pandemic.
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http://dx.doi.org/10.1136/bmjopen-2020-047900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907630PMC
February 2021

The effect of physical activity interventions on cognition function in patients with diabetes: A systematic review and meta-analysis.

Diabetes Metab Res Rev 2021 Feb 2:e3443. Epub 2021 Feb 2.

School of Public Health, Peking University, Beijing, China.

Background: In recent years, studies have revealed that cognition may be impaired by glucose metabolism disorder. Meanwhile, physical activity has been demonstrated to maintain blood glucose. This meta-analysis was conducted to assess the effect of physical activity on cognition in patients with diabetes and provide evidence for the treatment of cognition impairment among them.

Methods: We searched studies published in five databases from 1 January 1984 to 29 August 2020. A random-effect or fixed-effect meta-analysis was used to estimate the pooled effect of physical activity on the change of cognition throughout intervention duration and post-intervention cognition scores by standardized mean difference (SMD) and its 95% confidence interval (CI). We used funnel plots to evaluate the publication bias, I statistic to evaluate the heterogeneity and did subgroup analysis stratified by sample size and follow-up time.

Results: Five eligible studies involving 2581 patients with diabetes were included. The pooled effect of physical activity on cognition improvement in patients with diabetes was significant (SMD = 0.98, 95% CI: 0.34-1.62), while the effect on post-intervention cognition scores was not significant (SMD = 0.35, 95% CI: -0.04-0.73). In the subgroup analysis, the pooled effect was significantly higher in studies of follow-up time less than 1 year (SMD = 2.14, 95% CI: 1.63-2.64), while observing no significant effect in studies of follow-up time over 1 year (SMD = 0.10, 95% CI: -0.11-0.32).

Conclusions: Physical activity is beneficial to improving cognition in patients with diabetes. However, the long-term effect needs to be explored in future studies.
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http://dx.doi.org/10.1002/dmrr.3443DOI Listing
February 2021

Dietary Alpha-Ketoglutarate Promotes Epithelial Metabolic Transition and Protects Against DSS-Induced Colitis.

Mol Nutr Food Res 2021 Feb 5:e2000936. Epub 2021 Feb 5.

Q. Tian, A. B. Iniguez, Q. Sun, H. Wang, M.-J. Zhu, School of Food Science, Washington State University, Pullman, WA, 99164, USA.

Scope: As a natural compound in foods, alpha-ketoglutarate (aKG) is one of the key metabolites maintaining energy homeostasis. This study examined the beneficial effects of dietary aKG against the development of experimental colitis and further explored the underlying molecular mechanisms.

Methods And Results: Eight-week-old male C57BL/6 mice received drinking water with or without 1% aKG for four weeks. At week 3, colitis was induced by 2.5% dextran sulfate sodium (DSS) for 7 days followed by 7 days recovery. Dietary aKG supplementation decreased DSS-induced body weight loss, gross bleeding, fecal consistency score, and disease activity index. In agreement, aKG supplementation restored DSS-associated colon shortening, ameliorated mucosal damage and macrophage infiltration into colonic tissue, which were associated with suppressed gut inflammation and Wnt signaling, and improved epithelial structure. Consistently, aKG supplementation enhanced M1 to M2 macrophage polarization and strengthened intestinal barrier function. Additionally, aKG supplementation elevated colonic aKG levels while decreasing 2-hydroxyglutarate levels, which increased oxidative instead of glycolytic metabolism.

Conclusion: aKG supplementation protects against epithelial damage and ameliorates DSS- induced colitis, which were associated with suppressed inflammation, Wnt signaling pathway and glycolysis. Intake of foods enriched with aKG or aKG supplementation can be an alternative approach for the prevention or treatment of colitis that are common in Western societies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202000936DOI Listing
February 2021

In Situ Electrochemical Transformation Reaction of Ammonium-Anchored Heptavanadate Cathode for Long-Life Aqueous Zinc-Ion Batteries.

ACS Appl Mater Interfaces 2021 Feb 19;13(4):5034-5043. Epub 2021 Jan 19.

State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.

Rechargeable aqueous zinc-ion batteries (ZIBs) are promising portable and large-scale grid energy storage devices, as they are safe and economical. However, developing suitable ZIB cathode materials with excellent cycling performance characteristics remains a challenging task. Here, ammonium heptavanadate (NH)VO·3.2HO (NHVO) nanosquares with mixed-valence V/V as a cathode are developed for high-performance ZIBs. The layered NHVO shows a capacity of 362 mA h g at 0.05 A g, with a high energy density of 263.5 W h kg. It exhibits an initial specific capacity of 250.7 mA h g at a current density of 4 A g and retains 255 mA h g capacity after 1000 charge/discharge cycles. The VO-based cathode was demonstrated with a phase transition to the VO-based cathode upon initial cycling. Moreover, the in situ generated VO-based cathodes show excellent electrochemical properties, which provide a different perspective on the electrochemical reaction of cathode materials for aqueous ZIBs.
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http://dx.doi.org/10.1021/acsami.0c19309DOI Listing
February 2021

Maternal sleep quality during early pregnancy, risk factors and its impact on pregnancy outcomes: a prospective cohort study.

Sleep Med 2021 Mar 2;79:11-18. Epub 2021 Jan 2.

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China.

Objectives: We aimed to assess the prevalence of poor sleep quality during early pregnancy and its risk factors, and to explore the association between sleep quality and adverse pregnancy outcomes.

Methods: This was a prospective birth cohort study that included 4352 pregnant women. Sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI). The risk factors for poor sleep quality were analyzed by a logistic regression model. Log-binomial regression models were used to analyze the association between sleep quality and pregnancy outcomes.

Results: The prevalence of maternal poor sleep quality during early pregnancy was 34.14%. The multivariate logistic model showed that stillbirth history (OR = 2.45; 95% CI: 1.34, 4.47), history of induced abortion (OR = 1.26; 95% CI: 1.07, 1.49), general health-related quality of life (OR = 3.98; 95% CI: 2.97, 5.34), insufficient physical activity (OR = 1.18; 95% CI: 1.03, 1.36), smoking (OR = 1.59; 95% CI: 1.18, 2.15), and vegetarian (OR = 2.18; 95% CI: 1.54, 3.08) were risk factors for poor sleep quality, while taking folic acid consistently before pregnancy (OR = 0.83; 95% CI: 0.72,0.97) was the protective factor. After controlling for all the confounders, poor sleep quality during early pregnancy increased the risk of premature rupture of membranes by 12% (95% CI: 1.00, 1.25).

Conclusion: Pregnant women with a history of stillbirth and induced abortion, general health-related quality of life, insufficient physical activity, smoking, and a vegetarian diet tended to have poor sleep quality. More attention should be paid to healthy lifestyle of pregnant women to improve sleep quality and better pregnancy outcomes.
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http://dx.doi.org/10.1016/j.sleep.2020.12.040DOI Listing
March 2021

A Time-Frequency Measurement and Evaluation Approach for Body Channel Characteristics in Galvanic Coupling Intrabody Communication.

Sensors (Basel) 2021 Jan 6;21(2). Epub 2021 Jan 6.

College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China.

Intrabody communication (IBC) can achieve better power efficiency and higher levels of security than other traditional wireless communication technologies. Currently, the majority of research on the body channel characteristics of galvanic coupling IBC are motionless and have only been evaluated in the frequency domain. Given the long measuring times of traditional methods, the access to dynamic variations and the simultaneous evaluation of the time-frequency domain remains a challenge for dynamic body channels such as the cardiac channel. To address this challenge, we proposed a parallel measurement methodology with a multi-tone strategy and a time-parameter processing approach to obtain a time-frequency evaluation for dynamic body channels. A group search algorithm has been performed to optimize the crest factor of multitone excitation in the time domain. To validate the proposed methods, in vivo experiments, with both dynamic and motionless conditions were measured using the traditional method and the proposed method. The results indicate that the proposed method is more time efficient ( = 1 ms) with a consistent performance ( > 98%). Most importantly, it is capable of capturing dynamic variations in the body channel and provides a more comprehensive evaluation and richer information for the study of IBC.
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http://dx.doi.org/10.3390/s21020348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825556PMC
January 2021

Assembly of alternative prothrombinase by extracellular histones initiates and disseminates intravascular coagulation.

Blood 2021 Jan;137(1):103-114

Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Thrombin generation is pivotal to both physiological blood clot formation and pathological development of disseminated intravascular coagulation (DIC). In critical illness, extensive cell damage can release histones into the circulation, which can increase thrombin generation and cause DIC, but the molecular mechanism is not clear. Typically, thrombin is generated by the prothrombinase complex, comprising activated factor X (FXa), activated cofactor V (FVa), and phospholipids to cleave prothrombin in the presence of calcium. In this study, we found that in the presence of extracellular histones, an alternative prothrombinase could form without FVa and phospholipids. Histones directly bind to prothrombin fragment 1 (F1) and fragment 2 (F2) specifically to facilitate FXa cleavage of prothrombin to release active thrombin, unlike FVa, which requires phospholipid surfaces to anchor the classical prothrombinase complex. In vivo, histone infusion into mice induced DIC, which was significantly abrogated when prothrombin F1 + F2 were infused prior to histones, to act as decoy. In a cohort of intensive care unit patients with sepsis (n = 144), circulating histone levels were significantly elevated in patients with DIC. These data suggest that histone-induced alternative prothrombinase without phospholipid anchorage may disseminate intravascular coagulation and reveal a new molecular mechanism of thrombin generation and DIC development. In addition, histones significantly reduced the requirement for FXa in the coagulation cascade to enable clot formation in factor VIII (FVIII)- and FIX-deficient plasma, as well as in FVIII-deficient mice. In summary, this study highlights a novel mechanism in coagulation with therapeutic potential in both targeting systemic coagulation activation and correcting coagulation factor deficiency.
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http://dx.doi.org/10.1182/blood.2019002973DOI Listing
January 2021

Metabolism, absorption, and anti-cancer effects of sulforaphane: an update.

Crit Rev Food Sci Nutr 2021 Jan 4:1-17. Epub 2021 Jan 4.

Department of Animal Sciences, Washington State University, Pullman, Washington, USA.

Cancer is one of the most devastating diseases, and recently, a variety of natural compounds with preventive effects on cancer developments have been reported. Sulforaphane (SFN) is a potent anti-cancer isothiocyanate originating from (broccoli). SFN, mainly metabolized via mercapturic acid pathway, has high bioavailability and absorption. The present reviews mainly discussed the metabolism and absorption of SFN and newly discovered mechanistic understanding recent years for SFN's anti-cancer effects including promoting autophagy, inducing epigenetic modifications, suppressing glycolysis and fat metabolism. Moreover, its inhibitory effects on cancer stem cells and synergetic effects with other anti-cancer agents are also reviewed along with the clinical trials in this realm.
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http://dx.doi.org/10.1080/10408398.2020.1865871DOI Listing
January 2021

Association between sleep duration in early pregnancy and risk of gestational diabetes mellitus: a prospective cohort study.

Diabetes Metab 2020 Dec 16;47(5):101217. Epub 2020 Dec 16.

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China; Key Laboratory of Reproductive Health, National Health and Family Planning Commission of the People's Republic of China, Beijing, China.

Aims: As cohort studies of the impact of sleep duration during early pregnancy on gestational diabetes mellitus (GDM) are lacking, our study aimed to explore the association between sleep duration in the first trimester and GDM in one region of mainland China.

Methods: For this prospective cohort study, sleep duration data were collected from 3692 pregnant women at the first prenatal care appointment before 14 weeks of gestation. Multivariable log-binomial regression models were used to analyze the association of sleep duration with GDM after adjusting for demographic characteristics, health status (such as family history of diabetes, history of GDM, prepregnancy body mass index, gestational weight gain) and lifestyle habits (such as physical activity, dietary intakes).

Results: Our cohort included 166 (4.5%) short sleepers and 505 (14%) long sleepers. Shorter sleep duration was more likely to be observed in women aged ≥35 years who were multiparous, and had previous pregnancy, insufficient gestational weight gain, engaged in more vigorous physical activity, drank alcohol, were vegan and/or never took folic-acid supplements. Compared with normal sleepers (29%), the prevalence of GDM was significantly higher in short sleepers (38%; P = 0.01), but not in long sleepers (31%; P = 0.224). In the multivariable model, women with short sleep durations during early pregnancy had a 32% greater risk of GDM [adjusted risk ratio (aRR): 1.32, 95% CI: 1.06-1.63], whereas long sleepers did not (aRR: 1.09, 95% CI: 0.94-1.26).

Conclusion: Short sleep duration during early pregnancy is associated with an increased risk of GDM. This suggests that more attention should be paid to controlling the development of GDM in pregnant women with insufficient sleep.
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http://dx.doi.org/10.1016/j.diabet.2020.101217DOI Listing
December 2020

Plant extracts in prevention of obesity.

Crit Rev Food Sci Nutr 2020 Dec 15:1-14. Epub 2020 Dec 15.

Department of Animal Sciences, Washington State University, Pullman, Washington, USA.

Obesity has become a worldwide issue and is accompanied by serious complications. Western high energy diet has been identified to be a major factor contributing to the current obesity pandemic. Thus, it is important to optimize dietary composition, bioactive substances, and agents to prevent and treat obesity. To date, extracts from plants, such as vegetables, tea, fruits, and Chinese herbal medicine, have been showed to have the abilities of regulating adipogenesis and attenuating obesity. These plant extracts mainly contain polyphenols, alkaloids, and terpenoids, which could play a significant role in anti-obesity through various signaling pathways and gut microbiota. Those reported anti-obesity mechanisms mainly include inhibiting white adipose tissue growth and lipogenesis, promoting lipolysis, brown/beige adipose tissue development, and muscle thermogenesis. In this review, we summarize the plant extracts and their possible mechanisms responsible for their anti-obesity effects. Based on the current findings, dietary plant extracts and foods containing these bioactive compounds can be potential preventive or therapeutic agents for obesity and its related metabolic diseases.
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http://dx.doi.org/10.1080/10408398.2020.1852171DOI Listing
December 2020

Non-linear correlation between daily new cases of COVID-19 and meteorological factors in 127 countries.

Environ Res 2021 02 3;193:110521. Epub 2020 Dec 3.

Department of Epidemiology and Biostatics, School of Public Health, Peking University, No.38, Xueyuan Road, Haidian District, Beijing, 100191, China. Electronic address:

Meteorological parameters are the critical factors of affecting respiratory infectious disease such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and influenza, however, the effect of meteorological parameters on coronavirus disease 2019 (COVID-19) remains controversial. This study investigated the effects of meteorological factors on daily new cases of COVID-19 in 127 countries, as of August 31 2020. The log-linear generalized additive model (GAM) was used to analyze the effect of meteorological variables on daily new cases of COVID-19. Our findings revealed that temperature, relative humidity, and wind speed are nonlinearly correlated with daily new cases, and they may be negatively correlated with the daily new cases of COVID-19 over 127 countries when temperature, relative humidity and wind speed were below 20°C, 70% and 7 m/s respectively. Temperature(>20°C) was positively correlated with daily new cases. Wind speed (when>7 m/s) and relative humidity (>70%) was not statistically associated with transmission of COVID-19. The results of this research will be a useful supplement to help healthcare policymakers in the Belt and Road countries, the Centers for Disease Control (CDC) and the World Health Organization (WHO) to develop strategies to combat COVID-19.
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http://dx.doi.org/10.1016/j.envres.2020.110521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713195PMC
February 2021

Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis.

Cell Rep 2020 Dec;33(9):108461

Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA. Electronic address:

Although maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction.
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http://dx.doi.org/10.1016/j.celrep.2020.108461DOI Listing
December 2020

Production of recombinant butyrylcholinesterase from transgenic rice cell suspension cultures in a pilot-scale bioreactor.

Biotechnol Bioeng 2020 Nov 26. Epub 2020 Nov 26.

Department of Chemical Engineering, University of California, Davis, California, USA.

Producing recombinant proteins in transgenic plant cell suspension cultures in bioreactors provides controllability, reproducibility, scalability, and low-cost production, although low yields remain the major challenge. The studies on scaling-up to pilot-scale bioreactors, especially in conventional stainless-steel stirred tank bioreactors (STB), to produce recombinant proteins in plant cell suspension cultures are very limited. In this study, we scaled-up the production of rice recombinant butyrylcholinesterase (rrBChE), a complex hydrolase enzyme that can be used to prophylactically and therapeutically treat against organophosphorus nerve agents and pesticide exposure, from metabolically regulated transgenic rice cell suspension cultures in a 40-L pilot-scale STB. Employing cyclical operation together with a simplified-process operation (controlling gas sparging rate rather than dissolved oxygen and allowing natural sugar depletion) identified in lab-scale (5 L) bioreactor studies, we found a consistent maximum total active rrBChE production level of 46-58 µg/g fresh weight in four cycles over 82 days of semicontinuous operation. Additionally, maintaining the overall volumetric oxygen mass transfer coefficient (k a) in the pilot-scale STB to be equivalent to the lab-scale STB improves the maximum total active rrBChE production level and the maximum volumetric productivity to 85 µg/g fresh weight and 387 µg L  day , respectively, which are comparable to the lab-scale culture. Here, we demonstrate pilot-scale bioreactor performance using a metabolically regulated transgenic rice cell culture for long-term, reproducible, and sustained production of rrBChE.
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http://dx.doi.org/10.1002/bit.27638DOI Listing
November 2020

A new carbon emission reduction mechanism: Carbon Generalized System of Preferences (CGSP).

Environ Sci Pollut Res Int 2021 Jan 21;28(1):1267-1274. Epub 2020 Nov 21.

China Electronic Product Reliability and Environmental Testing Research Institute, Guangzhou City, 510000, Guangdong Province, China.

Countries throughout the whole world, including China, are working together to curb the greenhouse effect, but the effects seem very limited in spite of the fact that various low-carbon development strategies have been adopted, particularly in industrial enterprises. Therefore, carbon emissions caused by the public should be taken seriously, and the public should be encouraged to engage in behavior that limits carbon emissions. Therefore, this article introduces a new incentive mechanism called the Carbon Generalized System of Preferences (CGSP), which was first introduced in Guangdong Province, China. It is believed that this new mechanism matches the role of leadership in Guangdong in the urbanization and economic development of China by addressing the small sources of greenhouse gases (GHGs) and by issuing carbon coins. Compared with Chinese Certified Emission Reduction (CCER), the development scope, management level, and novel criteria of CGSP are very different but relatively easy for the public to accept. The CGSP shows that the network platform, reduced carbon emissions, and urban pilots are all compatible with the goals of the nation and city, and they promote the CGSP in different ways. Because of its consistency with ecological civilization in China, the prospect of the CGSP is bright; however, there are some challenges, such as policy and economic factors, combined with pollution control.
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http://dx.doi.org/10.1007/s11356-020-11670-7DOI Listing
January 2021

AMPKα1 regulates Idh2 transcription through H2B O-GlcNAcylation during brown adipogenesis.

Acta Biochim Biophys Sin (Shanghai) 2021 Jan;53(1):112-118

Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.

AMP-activated protein kinase (AMPK) is indispensable for the development and maintenance of brown adipose tissue (BAT), and its activity is inhibited due to obesity. The isocitrate dehydrogenase 2 (IDH2) is a mitochondrial enzyme responsible for the production of α-ketoglutarate, a key intermediate metabolite integrating multiple metabolic processes. We previously found that AMPKα1 ablation reduced cellular α-ketoglutarate concentration during brown adipocyte differentiation, but the effect of AMPKα1 on Idh2 expression remains undefined. In the present study, mouse C3H10T1/2 cells were transfected with Idh2-CRISPR/Cas9, and induced to brown adipogenesis. Our data suggested that brown adipogenesis was compromised due to IDH2 deficiency in vitro, which was accompanied by down-regulation of PR-domain containing 16. Importantly, the IDH2 content was reduced in brown stromal vascular cells (BSVs) separated from AMPKα1 knockout (KO) BAT, which was associated with lower contents of histone 2B (H2B) O-GlcNAcylation and monoubiquitination. Furthermore, both GlcNAcylated-H2B (S112) and ubiquityl-histone 2B (K120) contents in the Idh2 promoter were decreased in AMPKα1 KO BSVs. Meanwhile, ectopic O-linked N-acetylglucosamine transferase (OGT) expression was positively correlated with Idh2 expression, while OGT (T444A) mutation abolished the regulatory effect of AMPKα1 on Idh2. In vivo, reduced AMPKα1 activity and lower IDH2 abundance were observed in BAT of obese mice when compared with those in control mice. Taken together, our data demonstrated that IDH2 is necessary for brown adipogenesis and that AMPKα1 deficiency attenuates Idh2 expression, which might be by suppressing H2B O-GlcNAcylation modification.
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http://dx.doi.org/10.1093/abbs/gmaa136DOI Listing
January 2021

Effect of surgical margin on recurrence based on preoperative circulating tumor cell status in hepatocellular carcinoma.

EBioMedicine 2020 Dec 10;62:103107. Epub 2020 Nov 10.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P. R. China.. Electronic address:

Background: High rates of recurrence after resection severely worsen hepatocellular carcinoma (HCC) prognosis. This study aims to explore whether circulating tumor cell (CTC) is helpful in determine the appropriate liver resection margins for HCC patients.

Methods: HCC patients who underwent liver resection were enrolled into training (n=117) or validation (n=192) cohorts, then classified as CTC-positive (CTC≥1) or CTC-negative (CTC=0). A standardized pathologic sampling method was used in the training cohort to quantify microvascular invasion (mVI) and the farthest mVI from the tumor (FMT).

Findings: CTC number positively correlated with mVI counts (r=0.655, P<0.001) and FMT (r=0.495, P<0.001). The CTC-positive group had higher mVI counts (P=0.032) and greater FMT P=0.008) than the CTC-negative group. In the CTC-positive group, surgical margins of >1 cm independently protected against early recurrence (training cohort, P=0.004; validation cohort, P=0.001) with lower early recurrence rates (training cohort, 20.0% vs. 65.1%, P=0.005; validation cohort, 36.4% vs. 65.1%, P=0.003) compared to surgical margins of ≤1 cm. No differences in postoperative liver function were observed between patients with margins >1 cm vs. ≤1 cm. Surgical margin size minimally impacted early postoperative HCC recurrence in CTC-negative patients when using 0.5 cm or 1 cm as the threshold.

Interpretations: Preoperative CTC status predicts mVI severity in HCC patients and is a potential factor for determining optimal surgical margin size to ensure disease eradication and conserve liver function. A surgical margin of >1 cm should be achieved for patients with positive CTC.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgement section.
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http://dx.doi.org/10.1016/j.ebiom.2020.103107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658489PMC
December 2020

Prevalence and impact of diabetes in patients with COVID-19 in China.

World J Diabetes 2020 Oct;11(10):468-480

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly around the world. Previous studies have indicated that COVID-19 patients with diabetes are prone to having poor clinical outcomes.

Aim: To systematically evaluate the prevalence of diabetes among COVID-19 patients in China and its impact on clinical outcomes, including ICU admission, progression to severe cases, or death.

Methods: We searched studies published in PubMed, Web of Science, and EMBASE from December 1, 2019 to March 31, 2020 to identify relevant observational study that investigated the prevalence of diabetes among COVID-19 patients or its impact on clinical outcomes. We used a random-effects or fixed-effects model to estimate the pooled prevalence of diabetes and risk ratio (RR) and its 95% confidence interval (CI) of diabetes on outcomes. Funnel plots were used to evaluate the publication bias and the heterogeneity was evaluated by statistic.

Results: Twenty-three eligible articles including 49564 COVID-19 patients (1573 with and 47991 without diabetes) were finally included. The pooled prevalence of diabetes was 10% (95%CI: 7%-15%) in COVID-19 patients. In the subgroup analyses, the pooled prevalence of diabetes was higher in studies with patients aged > 50 years (13%; 95%CI: 11%-16%) than in studies with patients aged ≤ 50 years (7%; 95%CI: 6%-8%), in severe patients (17%; 95%CI: 14%-20%) than in non-severe patients (6%; 95%CI: 5%-8%), and in dead patients (30%; 95%CI: 13%-46%) than in survivors (8%; 95%CI: 2%-15%) ( < 0.05 for all). Compared with patients without diabetes, the risk of severe cases was higher (RR = 2.13, 95%CI: 1.76-2.56, = 49%) in COVID-19 patients with diabetes. The risk of death was also higher in COVID-19 patients with diabetes (RR = 3.16, 95%CI: 2.64-3.78, = 34%). However, diabetes was not found to be significantly associated with admission to ICU (RR = 1.16, 95%CI: 0.15-9.11).

Conclusion: Nearly one in ten COVID-19 patients have diabetes in China. Diabetes is associated with a higher risk of severe illness and death. The present study suggested that targeted early intervention is needed in COVID-19 patients with diabetes.
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http://dx.doi.org/10.4239/wjd.v11.i10.468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582115PMC
October 2020

bta-miR-23a Regulates the Myogenic Differentiation of Fetal Bovine Skeletal Muscle-Derived Progenitor Cells by Targeting MDFIC Gene.

Genes (Basel) 2020 Oct 20;11(10). Epub 2020 Oct 20.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

miR-23a, a member of the miR-23a/24-2/27a cluster, has been demonstrated to play pivotal roles in many cellular activities. However, the mechanisms of how bta-miR-23a controls the myogenic differentiation (MD) of PDGFRα bovine progenitor cells (bPCs) remain poorly understood. In the present work, bta-miR-23a expression was increased during the MD of bPCs. Moreover, bta-miR-23a overexpression significantly promoted the MD of bPCs. Luciferase reporter assays showed that the 3'-UTR region of (MyoD family inhibitor domain containing) could be a promising target of bta-miR-23a, which resulted in its post-transcriptional down-regulation. Additionally, the knockdown of by siRNA facilitated the MD of bPCs, while the overexpression of inhibited the activating effect of bta-miR-23a during MD. Of note, might function through the interaction between transcription factor and promoter. This study reveals that bta-miR-23a can promote the MD of bPCs through post-transcriptional downregulation of .
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http://dx.doi.org/10.3390/genes11101232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588927PMC
October 2020

Water Extract of Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

Front Nutr 2020 15;7:161. Epub 2020 Sep 15.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Bunge, as a traditional Chinese medicine, exhibits many phytochemical activities. The aim of the present study was to investigate the effects of Bunge water extract (PDBW) and its underlying mechanisms on gluconeogenesis and glycogen synthesis in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice. LC-MS/MS analyses of PDBW identified 6 major compounds including apigenin-7-O-β-D-glucoside, epicatechin, quercetin 3-O-β-D-glucuronide, kaempferol-3-O-β-D-glucopyranoside, scutellarin, and quercitrin. In the study, a mouse model of type 2 diabetes was induced by 4-week HFD combined with STZ (40 mg/kg body weight) for 5 days. After oral administration of PDBW at 400 mg/kg body weight daily for 8 weeks, the mice with type 2 diabetes showed significant decrease in the levels of fasting blood glucose and glycated hemoglobin A1c (HbA1c), and increase in the insulin level. PDBW improved the glucose tolerance, insulin sensitivity and lipid profiles. Furthermore, PDBW inhibited the mRNA levels of key gluconeogenic enzymes [phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)] in liver. PDBW also promoted glycogen synthesis by raising the liver glycogen content, decreasing the phosphorylation of glycogen synthase (GS) and increasing the phosphorylation of glycogen synthase kinase3β (GSK3β). Besides, PDBW induced the activation of protein kinase B (Akt) and AMP-activated protein kinase (AMPK), which might explain changes in the phosphorylation of above enzymes. In summary, PDBW supplementation ameliorates metabolic disorders in a HFD/STZ diabetic mouse model, suggesting the potential application of PDBW in prevention and amelioration of type 2 diabetes.
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http://dx.doi.org/10.3389/fnut.2020.00161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522508PMC
September 2020

Characterization of hepatitis B virus DNA integration patterns in intrahepatic cholangiocarcinoma.

Hepatol Res 2021 Jan 6;51(1):102-115. Epub 2020 Nov 6.

Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aim: Hepatitis B virus (HBV) integration is one of the mechanisms contributing to hepatocellular carcinoma (HCC) development. However, the status of HBV integration in intrahepatic cholangiocarcinoma (ICC) is poorly understood. This study aims to characterize the viral integration in HBV-related ICC.

Methods: The presence of HBV S and C gene in ICCs and the paratumor tissue was determined by polymerase chain reaction direct sequencing. Hepatitis B virus integration was detected by a high-throughput capture sequencing method. The expression analysis of the genes targeted by HBV in ICC was undertaken in The Cancer Genome Atlas dataset.

Results: Hepatitis B virus S and/or C gene fragments were detected in 71.43% (10/14) ICCs and 57.14% (8/14) paratumor tissues. Using the high-throughput capture sequencing approach, 139 and 183 HBV integration breakpoints were identified from seven ICC and seven paired paratumor tissues, respectively. Seven genes (TERT, CEACAM20, SPATA18, TRERF1, ZNF23, LINC01449, and LINC00486) were recurrently targeted by HBV-DNA in different ICC tissues or different cell populations of the same tissue. TERT, which is the most preferential HBV target gene in HCC, was found to be repeatedly interrupted by HBV-DNA in three different ICC tissues. Based on The Cancer Genome Atlas dataset, TERT, as well as three other HBV recurrently targeted genes (SPATA18, TRERF1, and ZNF23), showed differential expression levels between ICC and para-ICC tissues.

Conclusions: Taken together, HBV integration is a common event in HBV-related ICC. The HBV recurrent integration genes identified from this study, such as TERT, provide new clues for further research on the causative link between HBV infection and ICC.
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http://dx.doi.org/10.1111/hepr.13580DOI Listing
January 2021

Evaluation of Perioperative Complications in the Management of Biliary Atresia.

Front Pediatr 2020 28;8:460. Epub 2020 Aug 28.

Department of Pediatric Surgery, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Birth Defect, Shanghai, China.

To analyze the influence of perioperative complications in the management of biliary atresia (BA). A retrospective study was performed using a total of 422 BA patients who underwent Kasai portoenterostomy (KPE) in a single institution between February 2016 and May 2017. Data on patients' clinical characteristics, laboratory examinations, perioperative complications, and outcomes were collected. Unpaired two-tailed -test and χ test were employed for the comparison between BA patients with and without perioperative complications. Cox regression analysis was used to screen the risk factors for 2-years NLS in BA, and their influence on the 2-years NLS was analyzed using Kaplan-Meier survival analysis as well as the log-rank test. The incidence of perioperative complications, 6-months jaundice clearance (JC) and 2-years native liver survival (NLS) rate were 60.4, 59.5, and 56.6%, respectively. Patients with perioperative complications had lower serum albumin (ALB) level, but higher aspartate aminotransferase-to-platelet ratio index (APRI) and international normalized ratio (INR) levels when compared with those without perioperative complications (ALB, < 0.05; APRI, < 0.01; INR, < 0.05). Moreover, perioperative complications were correlated with glucocorticoid administration ( = 0.002). Univariate Cox regression analysis showed no relationship between perioperative complications and 2-years NLS ( > 0.05). However, multivariate Cox regression analysis indicated 6-months JC was an independent protective factor for 2-years NLS [ < 0.0001, hazard ratio (HR) = 0.074, 95% confidence interval = 0.05-0.11], and concordance index of this prediction model including age, weight, APRI, glucocorticoid, and 6-months JC was 0.811. Although perioperative complication is common during and after KPE, it had no influence on the prognosis of BA. However, assessment of the serum level of total bilirubin after KPE may serve as an important predictor for the outcome in BA.
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http://dx.doi.org/10.3389/fped.2020.00460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493688PMC
August 2020

Retinoic acid signalling in fibro/adipogenic progenitors robustly enhances muscle regeneration.

EBioMedicine 2020 Oct 24;60:103020. Epub 2020 Sep 24.

Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, and School of Molecular Bioscience, Washington State University, Pullman, WA. Electronic address:

Background: During muscle regeneration, excessive formation of adipogenic and fibrogenic tissues, from their respective fibro/adipogenic progenitors (FAPs), impairs functional recovery. Intrinsic mechanisms controlling the proliferation and differentiation of FAPs remain largely unexplored.

Methods: Here, we investigated the role of retinoic acid (RA) signalling in regulating FAPs and the subsequent effects on muscle restoration from a cardiotoxin-induced injury. Blockage of retinoic acid receptor (RAR) signalling was achieved through dominant negative retinoic acid receptor α (RARα403) expression specific in PDGFRα+ FAPs in vivo and by BMS493 treatment in vitro. Effects of RAR-signalling on FAP cellularity and muscle regeneration were also investigated in a high-fat diet-induced obese mice model.

Findings: Supplementation of RA increased the proliferation of FAPs during the early stages of regeneration while suppressing FAP differentiation and promoting apoptosis during the remodelling stage. Loss of RAR-signalling caused ectopic adipogenic differentiation of FAPs and impaired muscle regeneration. Furthermore, obesity disrupted the cellular transition of FAPs and attenuated muscle regeneration. Supplementation of RA to obese mice not only rescued impaired muscle fibre regeneration, but also inhibited infiltration of fat and fibrotic tissues during muscle repair. These beneficial effects were abolished after blocking RAR-signalling in FAPs of obese mice.

Interpretation: These data suggest that RAR-signalling in FAPs is a critical therapeutic target for suppressing differentiation of FAPs and facilitating the regeneration of muscle and other tissues.

Funding: This study was supported by grants from the National Institutes of Health (R01-HD067449 and R21-AG049976) to M.D.
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http://dx.doi.org/10.1016/j.ebiom.2020.103020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519288PMC
October 2020

Recent advances in cellulose-based membranes for their sensing applications.

Cellulose (Lond) 2020 Sep 11:1-23. Epub 2020 Sep 11.

Shaanxi Provincial Key Laboratory of Papermaking Technology and Specialty Paper Development, National Demonstration Center for Experimental Light Chemistry Engineering Education, Key Laboratory of Paper Based Functional Materials of China National Light Industry, Shaanxi University of Science and Technology, Xi'an, 710021 People's Republic of China.

Abstract: In recent years, sensing applications have played a very important role in various fields. As a novel natural material, cellulose-based membranes with many merits can be served as all kinds of sensors. This review summarizes the recent progress of cellulose membranes as sensors, mainly focusing on their preparation processes and sensing properties. In addition, the opportunities and challenges of cellulose membrane-based sensors are also prospected. This review provides some references for the design of cellulose membrane materials for sensing applications in the future.

Graphic Abstract:
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http://dx.doi.org/10.1007/s10570-020-03445-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483080PMC
September 2020

Impact of tumor necrosis factor inhibitors and methotrexate on diabetes mellitus among patients with inflammatory arthritis.

BMC Rheumatol 2020 2;4:39. Epub 2020 Sep 2.

Department of Medicine, Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, White Building Rm 5023, 3400 Spruce St, Philadelphia, PA 19104 USA.

Background: To determine whether initiation of a tumor necrosis factor inhibitor (TNFi) or methotrexate improves hemoglobin A1c in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) who also have diabetes mellitus (DM).

Methods: A retrospective cohort study was conducted in Optum's de-identified Clinformatics® Data Mart Database, an administrative claims database, using data from 2000 to 2014. Patients with PsA, RA, or AS, with DM (defined by ICD-9-CM codes) and/or HbA1c ≥7%, who newly initiated either a TNFi, MTX, or metformin (positive control) were identified. The change in HbA1c after drug initiation was calculated. Statistical differences in the change in HbA1c between drugs were assessed using the Wilcoxon rank sum test and linear regression models adjusting for potential confounders.

Results: Among 10,389 drug initiations in 9541 patients with PsA, RA, or AS, and available HbA1c values, HbA1c was ≥7 at baseline in 254 (35%) TNFi initiations, 361(37%) MTX initiations, and 2144 (50%) metformin initiations. Median HbA1c change was - 0.35 (IQR -1.10, 0.30) after TNFi initiation, - 0.40 (IQR -1.20, 0.30) after MTX initiation, and - 0.80 (IQR -1.60, - 0.10) after metformin initiation. In adjusted analyses, TNFi initiators had less of a decrease in HbA1c compared to MTX initiators (β 0.22, 95% CI: 0.004, 0.43),  = 0.046. Metformin initiators had a significantly greater decrease in HbA1c than MTX, β - 0.38 (95% CI: - 0.52, - 0.23),  < 0.001. Glucocorticoid use was not accounted for in the models.

Conclusion: HbA1c decreased with TNFi initiation or MTX initiation. Reductions in HbA1c after initiation of a TNFi or MTX are about half ( 0.4 units) the decrease observed after initiation of metformin.
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http://dx.doi.org/10.1186/s41927-020-00138-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466800PMC
September 2020

Euphnerins A and B, Diterpenoids with a 5/6/6 Rearranged Spirocyclic Carbon Skeleton from the Stems of .

J Nat Prod 2020 09 21;83(9):2592-2596. Epub 2020 Aug 21.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China.

Euphnerins A () and B (), two extremely modified diterpenoids possessing an unprecedented 5/6/6 rearranged spirocyclic carbon skeleton, and a biosynthetically related known diterpenoid () were purified from the stems of . Their structures were identified by NMR experiments and X-ray diffraction analysis, as well as experimental and calculated electronic circular dichroism data comparison. A putative biosynthetic relationship of and with their presumed precursor is proposed. Compound showed NO inhibitory effects in lipopolysaccharide-stimulated BV-2 cells with an IC value of 22.4 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00249DOI Listing
September 2020

Mechanism underlying the significant role of the miR-4262/SIRT1 axis in children with inflammatory bowel disease.

Exp Ther Med 2020 Sep 19;20(3):2227-2235. Epub 2020 Jun 19.

Department of Children's Gastroenterology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, P.R. China.

Inflammatory bowel disease (IBD) is a term used to describe chronic and recurrent gastrointestinal disease. In total, >2 million individuals worldwide have been diagnosed with IBD, including ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. There is accumulating evidence to indicate that microRNAs (miRNAs or miRs) are involved in the development and progression of IBD. miR-4262, an underlying promoter in tumor diseases, has been reported to regulate inflammatory responses. However, the potential mechanisms underlying the role of miR-4262 in IBD remain unknown. The present study attempted to explore the role and mechanisms of miR-4262 in IBD. Firstly, reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression of miR-4262 in 30 IBD colonic mucosa tissues, 30 normal tissues, 2% dextran sulfate sodium (DSS)-treated Caco-2 cells and normal cells. It was demonstrated that the expression levels of miR-4262 in IBD colonic mucosa tissues and 2% DSS-stimulated Caco-2 cells were markedly higher compared with those in the control groups. Target gene prediction databases and dual-luciferase reporter assays were then used, and sirtuin 1 (SIRT1) was identified as a target gene of miR-4262. Furthermore, the levels of SIRT1 in 2% DSS-stimulated Caco-2 cells and IBD colonic mucosa tissues were suppressed compared with the corresponding control groups. In addition, it was observed that miR-4262 negatively regulated SIRT1 expression in Caco-2 cells. Thereafter, Caco-2 cells were treated with inhibitor control, miR-4262 inhibitor, control-siRNA or SIRT1-siRNA for 48 h, followed by 2% DSS treatment for 4 days. The secretion of inflammatory factors was analyzed via ELISA and RT-qPCR. MTT assay, flow cytometry and western blot analysis were performed to assess cell viability, apoptosis and NF-κB signaling pathway-related protein levels, respectively. The results indicated that DSS enhanced the inflammatory response, suppressed cell viability and promoted cell apoptosis, and this was decreased following transfection with an miR-4262 inhibitor. In addition, 2% DSS upregulated p-p65 expression and enhanced the ratio of p-p65/p65, while the miR-4246 inhibitor exerted an opposite effect. All the effects of miR-4262 inhibitor on Caco-2 cells were eliminated following transfection with SIRT1-siRNA. It was thus concluded that miR-4262 may serve a role in the progression of IBD via targeting SIRT1, and miR-4262/SIRT1 may represent a potential target for the diagnosis and treatment of IBD.
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http://dx.doi.org/10.3892/etm.2020.8918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401569PMC
September 2020